EXCLUSIVE: Shape Therapeutics raises $112M in bid to make RNA editing — and a whole lot else — a reality
Two years after spinning out of CRISPR pioneer Prashant Mali’s lab, Shape Therapeutics has a lot more cash and a slightly new mission.
The company originally launched in 2019 with plans to develop therapies around a new form of gene editing, one they hoped could better address certain diseases than CRISPR or other forms of gene manipulations. That’s still their goal, but CEO Francois Vigneault has added a few others in the meantime.
“The company really started as, how can we find a solution to some of the limitations of gene editing?” Vigneault said. “But from there, we quickly realized there was a massive bottleneck in another sphere of gene therapy.”
Shape ended up spending considerable time and resources trying to develop and make broadly available solutions to two of the biggest constraints that have held up the broader field: manufacturing and delivery. They’ll now have a lot more money to do so and bring forward their own medicines, announcing a $112 million Series B on Thursday led by Decheng Capital and Breton Capital.
Shape specializes in RNA editing; the company tries to develop therapies that intercept the broken messages that the DNA of patients with certain diseases sends out and correct it before it gets turned into proteins. That contrasts with CRISPR and other gene editing approaches that try to directly — and permanently – alter DNA.
It does so by exploiting a naturally occurring enzyme that’s already present in human cells called ADAR. By sending in their own specially constructed strand of guide RNA, researchers can in theory recruit this enzyme and get it to manipulate specific strands of messenger RNA in particular ways. They could, for example, delete or add bases.
Shape is focusing their efforts on neurons, where ADAR seems to work particularly well — possibly because it’s naturally highly expressed — and where, by contrast, CRISPR companies have had particular difficulty applying their more well-known technology. They have lead programs in the rare genetic disease Rett syndrome and Parkinson’s.
In developing those therapies, Vigneault and his colleagues ran square into the problems every gene therapy company has hit during the field’s 2010s resurgence. The viral vectors used to shuttle genes (or in this case, RNA) are difficult to manufacture at scale. And it’s difficult to develop ones that go precisely to the right tissue and the right kind of cell in humans.
“We found this [technology] is a major advantage in neurons and CNS disorders,” Vigneault said. “But on the delivery front what we discover is a huge limitation.”
So Shape engineered a cell line they claim can produce more adeno-associated virus (AAV), the most common viral vector used in gene therapy, than any other method. And they invested in the technology to engineer AAVs, screening millions of AAVs in cells and monkeys to develop ones particularly suited to reaching neurons or muscles.
That puts Shape in direct competition with companies such as Affinia and Dyno, which are dedicated solely to AAV engineering and have raised hundreds of millions of dollars and signed billion-dollar deals with Big Pharma for their vectors.
Vigneault said Shape will similarly try to make their AAV and cell lines available to other groups in industry and academia, while continuing to develop their own therapies in house and with larger companies. They have broad ambitions there, too, recently updating their “pipeline” online to show, rather than the few programs closest to the clinic, a constellation of the dozens of diseases they believe their ADAR tech is best suited for, from Alzheimer’s to cystic fibrosis.
“The idea is to build a slightly different company than the typical one,” Vigneault said. “First make a tool that’s disruptive, not an incremental improvement, and when you have that tool, make it available so that you can help as many patients as possible because one company can’t do it all.”
Correction: The article has been to clarify Shape spun out of the Mali lab, not the Church lab.